Impacts of microphysical parameterizations on banded convective system in convection-permitting simulation: a case study

The representation of cloud microphysical processes in models has always been a challenge leading to uncertainty in convective simulations. This paper evaluates the effect of cloud microphysical parameterizations on the simulation of mesoscale convective systems (MCSs) through a realistic banded convection process. A series of numerical simulation experiments are performed using the Weather Research and Forecasting (WRF) model at a convection-permitting scale with a 3 km horizontal grid spacing. Specifically, four experiments considering different hydrometeor species within the WRF single-moment-microphysics schemes (WSMMPs) are conducted, and three additional sensitivity tests change the graupel particle properties. The results indicate that the significant differences in the times of convection initiation across the experiments reach 120 min, and more hydrometeor species may lead to later convection initiation. Moreover, the frozen graupel hydrometeor characteristics can appreciably alter the simulated convective morphology, even more than other hydrometeor species. When the graupel becomes smaller (such as Graupel-like), the fall speed of the graupel particles decreases. Therefore, more numerous graupel particles reside in clouds for a longer time, and experience more atmospheric diabatic heating and cooling effects. As a result, the simulated convective systems exhibit strong banded convective echo characteristics, the surface 10-m wind gust increases, and the cold pools associated with additional melting and evaporation become stronger, accelerating the propagation of the system. In contrast, larger and less abundant graupels (e.g., Hail-like) have a faster fall speed, and the atmospheric diabatic heating and cooling decrease by shortening the duration of their residence time within the clouds, resulting in a weak quasi-linear convective system, weak surface 10-m wind gust, unobvious cold pool, and slower propagation. Comparisons of the experiments further demonstrate that the fall speeds of frozen graupel particles largely impact the vertical distribution of the hydrometeors and the related microphysical processes

Locally advanced rectal cancer with dMMR/MSI-H may be excused from surgery after neoadjuvant anti-PD-1 monotherapy: a multiple-center, cohort study

ObjectiveExamine patients with locally advanced rectal cancer (LARC) with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) who received neoadjuvant immunotherapy (nIT), and compare the outcomes of those who chose a watch-and-wait (WW) approach after achieving clinical complete response (cCR) or near-cCR with those who underwent surgery and were confirmed as pathological complete response (pCR).MethodsLARC patients with dMMR/MSI-H who received nIT were retrospectively examined. The endpoints were 2-year overall survival (OS), 2-year disease-free survival (DFS), local recurrence (LR), and distant metastasis (DM). The efficacy of programmed cell death protein-1 (PD-1) inhibitor, immune-related adverse events (irAEs), surgery-related adverse events (srAEs), and enterostomy were also recorded.ResultsTwenty patients who received a PD-1 inhibitor as initial nIT were examined. Eighteen patients (90%) achieved complete response (CR) after a median of 7 nIT cycles, including 11 with pCR after surgery (pCR group), and 7 chose a WW strategy after evaluation as cCR or near-cCR (WW group). Both groups had median follow-up times of 25.0 months. Neither group had a case of LR or DM, and the 2-year DFS and OS in each group was 100%. The two groups had similar incidences of irAEs (P=0.627). In the pCR group, however, 2 patients (18.2%) had permanent colostomy, 3 (27.3%) had temporary ileostomy, and 2 (18.2%) had srAEs.ConclusionNeoadjuvant PD-1 blockade had high efficacy and led to a high rate of CR in LARC patients with dMMR/MSI-H. A WW strategy appears to be a safe and reliable option for these patients who achieve cCR or near-cCR after nIT

Prognostic and Clinicopathological Value of PINX1 in Various Human Tumors: A Meta-Analysis

PINX1 (Pin2/TRF1 interacting protein X1, an intrinsic telomerase inhibitor and putative tumor suppressor gene) may represent a novel prognostic tumor biomarker. However, the results of previous studies are inconsistent and the prognostic value of PINX1 remains controversial. Therefore, we conducted a meta-analysis to determine whether PINX1 expression is associated with overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), recurrence-free survival (RFS), and clinicopathological characteristics in patients with malignant tumors. A systematic search was performed in the PubMed, Web of Science, and Embase databases in April 2018. Quality assessment was performed according to the modified Newcastle-Ottawa Scale. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95.0% confidence intervals (CIs) were calculated to determine the relationship between PINX1 expression and OS, DSS, DFS/RFS, and clinicopathological characteristics. Due to the heterogeneity across the included studies, subgroup and sensitivity analyses were performed. Fixed-effects models were used when the heterogeneity was not significant and random-effects models were used when the heterogeneity was significant. Fourteen studies of 16 cohorts including 2,624 patients were enrolled. Low PINX1 expression was associated with poor OS (HR: 1.51, 95.0% CI: 1.03–2.20; P = 0.035) and DFS/RFS (HR: 1.78, 95.0% CI: 1.28–2.47; P = 0.001) but not DSS (HR: 0.80, 95.0% CI: 0.38–1.67; P = 0.548). Low PINX1 expression was also associated with lymphatic invasion (OR: 2.23, 95.0% CI: 1.35–3.70; P = 0.002) and advanced tumor-node-metastasis stage (OR: 2.43, 95.0% CI: 1.29–4.57; P = 0.006). No significant associations were observed between low PINX1 expression and sex, depth of invasion, grade of differentiation, and distant metastasis. Low PINX1 expression was associated with poor OS and DFS/RFS and lymphatic invasion and advanced tumor-node-metastasis stage, suggesting that PINX1 expression may be a useful predictor of prognosis in patients with malignant tumors

Predictive role of ctDNA in esophageal squamous cell carcinoma receiving definitive chemoradiotherapy combined with toripalimab

Abstract The combination of toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) demonstrated encouraging efficacy against locally advanced esophageal squamous cell carcinoma (ESCC) in the EC-CRT-001 phase II trial (NCT04005170). The primary endpoint of this trial was the clinical complete response rate (cCR), and the secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response, and quality of life. The exploratory analyses of EC-CRT-001 include exploring the role of circulating tumor DNA (ctDNA) and blood-based tumor mutational burden (bTMB) in predicting the response and survival. In total, 118 blood and 35 tissue samples from 42 enrolled patients were included in the analyses. We found that ctDNA-negative patients achieved a higher cCR compared to those with detectable ctDNA during CRT (83%, 19/23 vs. 39%, 7/18; p = 0.008) or post-CRT (78%, 21/27 vs. 30%, 3/10; p = 0.017). Patients with detectable ctDNA during CRT had shorter PFS (p = 0.014). Similarly, patients with post-CRT detectable ctDNA had a significantly shorter PFS (p = 0.012) and worse OS (p = 0.004). Moreover, patients with high bTMB levels during CRT had prolonged OS (p = 0.027). In conclusion, ctDNA and bTMB have the potential to predict treatment efficacy and survival in ESCC treated with CRT and immunotherapy

Effects of Noncovalent Interactions on High-Spin Fe(IV)–Oxido Complexes

High-valent nonheme FeIV-oxido species are key intermediates in biological oxidation, and their properties are proposed to be influenced by the unique microenvironments present in protein active sites. Microenvironments are regulated by noncovalent interactions, such as hydrogen bonds (H-bonds) and electrostatic interactions; however, there is little quantitative information about how these interactions affect crucial properties of high valent metal-oxido complexes. To address this knowledge gap, we introduced a series of FeIV-oxido complexes that have the same S = 2 spin ground state as those found in nature and then systematically probed the effects of noncovalent interactions on their electronic, structural, and vibrational properties. The key design feature that provides access to these complexes is the new tripodal ligand [poat]3-, which contains phosphinic amido groups. An important structural aspect of [FeIVpoat(O)]- is the inclusion of an auxiliary site capable of binding a Lewis acid (LAII); we used this unique feature to further modulate the electrostatic environment around the Fe-oxido unit. Experimentally, studies confirmed that H-bonds and LAII s can interact directly with the oxido ligand in FeIV-oxido complexes, which weakens the Fe═O bond and has an impact on the electronic structure. We found that relatively large vibrational changes in the Fe-oxido unit correlate with small structural changes that could be difficult to measure, especially within a protein active site. Our work demonstrates the important role of noncovalent interactions on the properties of metal complexes, and that these interactions need to be considered when developing effective oxidants

Ultrafast growth of single-crystal graphene assisted by a continuous oxygen supply

Graphene has a range of unique physical properties(1,2) and could be of use in the development of a variety of electronic, photonic and photovoltaic devices(3-5). For most applications, large-area high-quality graphene films are required and chemical vapour deposition (CVD) synthesis of graphene on copper surfaces has been of particular interest due to its simplicity and cost effectiveness(6-15). However, the rates of growth for graphene by CVD on copper are less than 0.4 mu m s(-1), and therefore the synthesis of large, single-crystal graphene domains takes at least a few hours. Here, we show that single-crystal graphene can be grown on copper foils with a growth rate of 60 mu m s(-1). Our high growth rate is achieved by placing the copper foil above an oxide substrate with a gap of similar to 15 mu m between them. The oxide substrate provides a continuous supply of oxygen to the surface of the copper catalyst during the CVD growth, which significantly lowers the energy barrier to the decomposition of the carbon feedstock and increases the growth rate. With this approach, we are able to grow single-crystal graphene domains with a lateral size of 0.3 mm in just 5 s.ope